Chromatin accessibility landscape of relapsed pediatric B-lineage acute lymphoblastic leukemia.
Han WangHuiying SunBilin LiangFang ZhangFan YangBowen CuiLixia DingXiang WangRonghua WangJiaoyang CaiYanjing TangJianan RaoWenting HuShuang ZhaoWenyan WuXiaoxiao ChenKefei WuJunchen LaiYangyang XieBenshang LiJingyan TangShuhong ShenYu LiuPublished in: Nature communications (2023)
For around half of the pediatric B-lineage acute lymphoblastic leukemia (B-ALL) patients, the molecular mechanism of relapse remains unclear. To fill this gap in knowledge, here we characterize the chromatin accessibility landscape in pediatric relapsed B-ALL. We observe rewired accessible chromatin regions (ACRs) associated with transcription dysregulation in leukemia cells as compared with normal B-cell progenitors. We show that over a quarter of the ACRs in B-ALL are in quiescent regions with high heterogeneity among B-ALLs. We identify subtype-specific and allele-imbalanced chromatin accessibility by integrating multi-omics data. By characterizing the differential ACRs between diagnosis and relapse in B-ALL, we identify alterations in chromatin accessibility during drug treatment. Further analysis of ACRs associated with relapse free survival leads to the identification of a subgroup of B-ALL which show early relapse. These data provide an advanced and integrative portrait of the importance of chromatin accessibility alterations in tumorigenesis and drug responses.
Keyphrases
- acute lymphoblastic leukemia
- free survival
- transcription factor
- dna damage
- gene expression
- single cell
- genome wide
- acute myeloid leukemia
- allogeneic hematopoietic stem cell transplantation
- electronic health record
- diffuse large b cell lymphoma
- newly diagnosed
- healthcare
- induced apoptosis
- dna methylation
- ejection fraction
- prognostic factors
- oxidative stress
- hodgkin lymphoma
- emergency department
- randomized controlled trial
- multiple myeloma
- clinical trial
- cell cycle arrest
- signaling pathway
- cell proliferation
- artificial intelligence
- study protocol
- replacement therapy
- data analysis
- chronic kidney disease
- phase iii
- open label
- pi k akt